Preferential magnetic targeting of carbon nanotubes to cancer sites: noninvasive tracking using MRI in a murine breast cancer model

Preferential magnetic targeting of carbon nanotubes to cancer sites: noninvasive tracking using MRI in a murine breast cancer model
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DOI:
10.2217/nnm.14.145
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发表时间:
2015-01-01
期刊:
影响因子:
5.5
通讯作者:
Al Sayed, Baraa
Al Sayed, Baraa
中科院分区:
医学3区
文献类型:
--
作者:
Al Faraj, Achraf;Shaik, Asma Sultana;Al Sayed, Baraa

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目的:本研究评估了在4t1诱导的乳腺癌小鼠模型中单壁碳纳米管(SWCNTs)磁性靶向的改善,并将其与与特异性抗体结合的活性靶向SWCNTs作为药物递送纳米载体的潜在应用进行了比较。材料与方法:研究了负载氧化铁纳米颗粒的聚乙烯吡咯烷酮SWCNTs,利用优化的柔性磁体放置在肿瘤部位上,以改善其磁共振检测和磁铁吸引力。它们同样与内啡肽/CD105抗体偶联,用于SWCNTs的活性靶向。然后对无创MRI方案进行了优化,以实现肿瘤部位的体内成像、SWCNTs的敏感检测和表观扩散系数的测量。对所使用的SWCNTs的生物相容性进行了特别关注。结果:铁标记的SWCNTs表现出非常高的磁共振r2*弛豫度,允许使用无创MRI进行敏感检测,并使用磁铁增强靶向性。生物相容性评价证实了它们在动物用药中的安全性。T2*和表观扩散系数的测量结果都证实了它们的磁性靶向性从注射后2小时开始增强,而铁标记的SWCNT + CD105样品从注射后24小时开始观察到抗体偶联活性靶向性的增强,但具有统计学意义。结论:这些结果证明了磁靶向特异性递送高负荷铁标记SWCNTs作为癌症治疗的新型纳米载体的效率,并允许使用无创MRI对其进行敏感检测。
Aim: This study evaluated the improvement in magnetic targeting of single-walled carbon nanotubes (SWCNTs) in a 4T1-induced breast cancer murine model and compared their enhanced delivery with active targeted SWCNTs conjugated with a specific antibody for prospective applications as drug-delivery nanocarriers. Materials & methods: Polyvinylpyrrolidone SWCNTs, loaded with iron oxide nanoparticles to improve their magnetic resonance detection and magnet attraction using an optimized flexible magnet positioned over the tumor site were developed. They were equally conjugated with Endoglin/CD105 antibody for SWCNTs active targeting. A noninvasive MRI protocol was then optimized to allow in vivo imaging of tumor site, sensitive detection of SWCNTs and apparent diffusion coefficient measurements. Special focus was devoted to evaluate the biocompatibility of the used SWCNTs. Results: Iron-tagged SWCNTs exhibited very high magnetic resonance r2* relaxivities allowing their sensitive detection using noninvasive MRI and enhanced targeting using the magnet. Biocompatibility evaluations confirmed their safety for animal administration. Both T2* and apparent diffusion coefficient measurements confirmed their enhanced magnetic targeting starting from 2 h postinjection while a lower, but statistically significant enhanced targeting of antibody-conjugated active targeting was observed starting from 24 h postinjection of iron-tagged SWCNT + CD105 samples. Conclusion: These results demonstrate the efficiency of magnetic targeting to specifically deliver higher load of iron-tagged SWCNTs as novel nanocarriers for cancer theranostics and allow their sensitive detection using noninvasive MRI.